۱۱β-Hydroxysteroid dehydrogenase type ۱ amplifies inflammation in LPS-induced THP-۱ cells

Lingli Luo; Dongmei Zhu; Zheng Zhang; Hanjie Zeng; Min Huang; Suming Zhou

۱۱β-Hydroxysteroid dehydrogenase type ۱ amplifies inflammation in LPS-induced THP-۱ cells

محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 26، شماره: 3

سال انتشار: 1402

نوع سند: مقاله ژورنالی

زبان: انگلیسی

مشاهده: 185

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لینک ثابت به این مقاله:

https://civilica.com/doc/1594940

شناسه ملی سند علمی:

JR_IJBMS-26-3_015

تاریخ نمایه سازی: 8 بهمن 1401

چکیده مقاله:

Objective(s): The role of glucocorticoids as anti-inflammatory and immune-stimulatory drugs has been widely reported. However, the role of ۱۱β-hydroxysteroid dehydrogenase type ۱ (۱۱β-HSD۱), which catalyzes the conversion of inactive cortisone into active cortisol, in inflammation remains unclear. This study aimed to examine the mechanism of actions of ۱۱β-HSD۱ in lipopolysaccharide (LPS)-induced THP-۱ cells.Materials and Methods: The gene expression of ۱۱β-HSD۱ and pro-inflammatory cytokines was detected via RT-PCR. The protein expression of IL-۱β in cell supernatants was detected via ELISA. Oxidative stress and mitochondrial membrane potential were assessed using a reactive oxygen species (ROS) kit and a mitochondrial membrane potential (MMP) kit, respectively. The expression of Nuclear Factor- Kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) was detected via western blotting.Results: Elevated levels of ۱۱β-HSD۱ contributed to the expression of inflammatory cytokines, whereas BVT.۲۷۳۳, a selective ۱۱β-HSD۱ inhibitor, ameliorated inflammatory responses, ROS, and mitochondrial damage in LPS-stimulated THP-۱ cells. Furthermore, cortisone and cortisol, which are the substrate and product of ۱۱β-HSD۱, respectively, showed biphasic responses and induced the expression of pro-inflammatory cytokines at a low concentration in both LPS-stimulated or untreated THP-۱ cells. The enhanced inflammation was attenuated by co-treatment with BVT.۲۷۳۳ and the glucocorticoid receptor (GR) antagonist RU۴۸۶, but not in those treated with the mineralocorticoid receptor (MR) antagonist spironolactone. Overall, the results indicate that ۱۱β-HSD۱ amplifies inflammatory responses by activating the NF-κB and MAPK signaling pathways.Conclusion: Inhibition of ۱۱β-HSD۱ may serve as a potential therapeutic target against the excessive activation of inflammation.

کلیدواژه ها:

۱۱β-Hydroxysteroid- dehydrogenase type ۱ ، BVT.۲۷۳۳ ، Glucocorticoid Inflammation ، THP-۱ cells

نویسندگان

Lingli Luo